Apoptosis is the biochemical program Applicants' bodies utilize to remove unwanted, damaged, or diseased cells. Deregulation of this process is required for cancer development and serves as a major barrier to effective treatment. Recent evidence suggests that one or more components of apoptotic signaling are disrupted in all human cancers, either by genetic mutation of genes encoding core apoptotic machinery or by other mechanisms (e.g. epigenetic mechanisms or upstream oncogenic mutations). These genetic changes provide cancer cells with a survival advantage, ensuring their uncontrolled growth. Despite the important role of apoptosis in the development and maintenance of cancer, few therapeutics targeting apoptotic signaling have reached clinical evaluation. The compositions and methods provided address these and other needs in the art.